2278 Conclusions
The serpinin family of peptides is the newest set of biologically active peptides
found to be derived from processing of CgA. The cleavage of the penultimate pair
of basic residues at the C-terminus to generate this set of peptides appears to occur
first in the processing of CgA, since the remaining intact part of the CgA minus the
C-terminus was readily isolated in adrenal medulla extract since 1988 (Wohlfarter
et al. 1988 ). Nevertheless, the liberated C-terminal peptide fragment was not iso-
lated till 2011 (Koshimizu et al. 2011a). While serpinin, pGlu-serpinin and serpinin-
RRG are the forms that we have found differentially expressed in various tissues,
there may be still other members of the serpinin family that have biological activity.
These three members of serpinin peptides have diverse functions from regulation of
granule biogenesis through up-regulation of a protease inhibitor, PN-1; protection
against cell death through increasing BCL2 expression; and anti-angiogenesis activ-
ity. pGlu-serpinin appears to be the most potent in these functions except in anti-
angiogenesis where serpinin-RRG had the strongest effect. The mechanism of
action of serpinin-RRG in promoting anti-angiogensis has yet to be explored. The
presence of pGlu-serpinin in areas of the CNS enriched in nerve fibers or terminals
and the glomerular layer of the olfactory bulb, and in the retina suggest that this
peptide could be an important neurotransmitter or neuromodulator in certain sys-
tems. Future work should focus on finding the receptor for the serpinin peptides,
investigating a possible neurotransmitter/neuromodulator role and exploring new
roles of these peptides in the endocrine and neuronal systems, as well as in metabo-
lism. Finally given the strong activity of pGlu-serpinin in enhancing myocardial
contractility and relaxation, this peptide could be an excellent therapeutic agent
since its effect does not affect blood pressure (Tota et al. 2012 ).
Acknowledgements This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National
Institutes of Health, USA
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Serpinin Peptides: Tissue Distribution and Functions